We provide national-scale experimental evidence from China showing that transparency by local governments improves the management of air pollution. Governments that perform better have more reasons to be transparent, making the causal relationship between transparency and policy outcomes difficult to disentangle. In 2015, we randomly assigned municipal governments in China to a high-visibility, public rating of their adherence to national requirements for transparency about their regulation of pollution. By 2016, this treatment significantly boosted transparency in treated cities relative to control cities, allowing us to observe the effect of randomly increasing transparency in the years that followed. Subsequently, high-polluting firms in treated cities cut their violations by 37% compared to similar firms in control cities. Inspections by local governments increased by about 90% in treated cities relative to control cities. Ambient air pollution decreased between 8 and 10% in treated cities relative to control cities, which likely generated significant health benefits. This study provides strong evidence that governmental transparency causes improved environmental quality, at least in a setting where the public and higher governments want to hold local governments accountable.
The mosquito Aedes aegypti infects hundreds of millions of people annually with disease-causing viruses. When a mosquito approaches a host, the host often swats defensively. Here, we reveal the mosquito's escape behavior during host seeking in response to a threatening visual cue-a newly appearing shadow. We found that reactions to a shadow are far more aversive when it appears quickly versus slowly. Remarkably, mosquitoes evade shadows under very dim light conditions. Knockout of the TRP channel compromises the ability of mosquitoes to avoid threatening shadows, but only under high light conditions. Conversely, removing two of the five rhodopsins normally present in the compound eyes, Op1 and Op2, diminishes shadow aversion, but only under low light. Upon removal of a threatening visual cue, mosquitoes quickly re-initiate host seeking. Thus, female Aedes balance their need to host seek with visual threat avoidance by rapidly transitioning between these two behavioral states.
Many in the autistic community have expressed concerns regarding the use of behavioral interventions with autistic children, suggesting that these interventions may not be socially valid. Though behavioral interventions have evolved to be more naturalistic and child-centered, little structured research has been done to explicitly seek autistic perspectives on the acceptability of specific components of behavioral interventions. Autistic adults (N = 235) were recruited online to take the Autism Intervention Attitudes Scale (AIAS), a questionnaire designed to gather feedback on common intervention goals and practices. Results indicate that participants find goals and practices that highlight quality of life, safety, and autistic interactions acceptable, while those that focus on normalization based on neurotypical standards are not. An exploratory graph analysis revealed three communities of goals (uncontroversial goals, controversial goals, and social goals). Comparison between naturalistic and structured intervention components additionally showed that autistic participants favored naturalistic strategies. These findings are in line with known criticisms of behavioral intervention from autistic adults, but also provide more information on the specific ways in which behavioral interventions can be reformed. This information can guide professionals in the development of appropriate goals and decisions around intervention planning.
Many behavioral responses to climate change are carbon-intensive, raising concerns that adaptation may cause additional warming. The sign and magnitude of this feedback depend on how increased emissions from cooling balance against reduced emissions from heating across space and time. We present an empirical approach that forecasts the effect of future adaptive energy use on global average temperature over the 21st century. We estimate that energy-based adaptation will lower global mean surface temperature in 2099 by 0.07 to 0.12 °C relative to baseline projections under Representative Concentration Pathways 4.5 and 8.5. This cooling avoids 0.6 to 1.8 trillion U.S. Dollars ($2019) in damages, depending on the baseline emissions scenario. Energy-based adaptation lowers business-as-usual emissions for 85% of countries, reducing the mitigation required to meet their unilateral Nationally Determined Contributions by 20% on average. These findings indicate that while business-as-usual adaptive energy use is unlikely to accelerate warming, it raises important implications for countries existing mitigation commitments.
BACKGROUND: De novo DNA methylation by DNMT3A is a fundamental epigenetic modification for transcriptional regulation. Histone tails and regulatory proteins regulate DNMT3A, and the crosstalk between these epigenetic mechanisms ensures appropriate DNA methylation patterning. Based on findings showing that Fos ecRNA inhibits DNMT3A activity in neurons, we sought to characterize the contribution of this regulatory RNA in the modulation of DNMT3A in the presence of regulatory proteins and histone tails. RESULTS: We show that Fos ecRNA and mRNA strongly correlate in primary cortical neurons on a single cell level and provide evidence that Fos ecRNA modulation of DNMT3A at these actively transcribed sites occurs in a sequence-independent manner. Further characterization of the Fos ecRNA-DNMT3A interaction showed that Fos-1 ecRNA binds the DNMT3A tetramer interface and clinically relevant DNMT3A substitutions that disrupt the inhibition of DNMT3A activity by Fos-1 ecRNA are restored by the formation of heterotetramers with DNMT3L. Lastly, using DNMT3L and Fos ecRNA in the presence of synthetic histone H3 tails or reconstituted polynucleosomes, we found that regulatory RNAs play dominant roles in the modulation of DNMT3A activity. CONCLUSION: Our results are consistent with a model for RNA regulation of DNMT3A that involves localized production of short RNAs binding to a nonspecific site on the protein, rather than formation of localized RNA/DNA structures. We propose that regulatory RNAs play a dominant role in the regulation of DNMT3A catalytic activity at sites with increased production of regulatory RNAs.
Innate immune response cells produce high concentrations of the free radical nitric oxide (NO) in response to pathogen infection. The antimicrobial properties of NO include nonspecific damage to essential biomolecules and specific inactivation of enzymes central to aerobic metabolism. However, the molecular targets of NO in anaerobic metabolism are less understood. Here, we demonstrate that the Escherichia coli glycyl radical enzyme pyruvate formate lyase (PFL), which catalyzes the anaerobic metabolism of pyruvate, is irreversibly inhibited by NO. Using electron paramagnetic resonance and site-directed mutagenesis we show that NO destroys the glycyl radical of PFL. The activation of PFL by its cognate radical S-adenosyl-l-methionine-dependent activating enzyme (PFL-AE) is also inhibited by NO, resulting in the conversion of the essential iron-sulfur cluster to dinitrosyl iron complexes. Whole-cell EPR and metabolic flux analyses of anaerobically growing E. coli show that PFL and PFL-AE are inhibited by physiologically relevant levels of NO in bacterial cell cultures, resulting in diminished growth and a metabolic shift to lactate fermentation. The class III ribonucleotide reductase (RNR) glycyl radical enzyme and its corresponding RNR-AE are also inhibited by NO in a mechanism analogous to those observed in PFL and PFL-AE, which likely contributes to the bacteriostatic effect of NO. Based on the similarities in reactivity of the PFL/RNR and PFL-AE/RNR-AE enzymes with NO, the mechanism of inactivation by NO appears to be general to the respective enzyme classes. The results implicate an immunological role of NO in inhibiting glycyl radical enzyme chemistry in the gut.
This study develops an event-based, energy-efficient control strategy for desynchronizing coupled neuronal networks using optimal control theory. Inspired by phase resetting techniques in Parkinsons disease treatment, we incorporate stochasticity of the systems dynamics into deterministic models to address neural system intrinsic noise. We use an advanced computational solver for nonlinear stochastic partial differential equations to solve the stochastic Hamilton-Jacobi-Bellman equation via level set methods for a single neuron model; this allows us to find control inputs which drive the dynamics close to the systems phaseless set. When applied to coupled neuronal networks, these inputs achieve effective randomization of neuronal spike timing, leading to significant network desynchronization. Compared to its deterministic counterpart, our stochastic method can achieve considerable energy savings. The event-based control minimizes unnecessary charge transfer, potentially extending implanted stimulator battery life while maintaining robustness against variations in neuronal coupling strengths and network heterogeneities. These findings highlight the potential for developing energy-efficient neurostimulation techniques with implications for deep brain stimulation protocols. The presented computational framework could also be applied to other domains for which stochastic optimal control problems are prevalent.
The goal of this protocol is to improve the characterization and performance standardization of multiphoton microscopy hardware across a large user base. We purposefully focus on hardware and only briefly touch on software and data analysis routines where relevant. Here we cover the measurement and quantification of laser power, pulse width optimization, field of view, resolution and photomultiplier tube performance. The intended audience is scientists with little expertise in optics who either build or use multiphoton microscopes in their laboratories. They can use our procedures to test whether their multiphoton microscope performs well and produces consistent data over the lifetime of their system. Individual procedures are designed to take 1-2 h to complete without the use of expensive equipment. The procedures listed here help standardize the microscopes and facilitate the reproducibility of data across setups.
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